Design of enkephalin modifications protected from brain extracellular peptidases providing long-term analgesia.

•Many therapeutic peptides are ineffective because of rapid destruction by peptidases.•In brain the exopeptidases exist that cannot break the bonds formed by β-alanine.•Peptides with β-alanine on their ends are protected from these enzymes.•Similarly modified forms of enkephalin showing prolonged anesthesia are designed.•These enkephalin forms are not toxic and show no negative influence on memory.